Whole transcriptome analysis of Mycobacterium avium subsp. paratuberculosis infection and identification of circulating miRNA as biomarkers for resilience

Abstract Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne’s disease (JD), results in a chronic enteritis affecting ruminants worldwide and presents to severe economic and welfare issues. Pathogenic mycobacteria such as MAP are able to manipulate host transcriptomic pathways to establish infection and cause disease. Following exposure to pathogenic mycobacteria, host microRNA (miRNA) are modulated, effecting downstream gene expression. miRNA have been utilised as circulating biomarkers for several human diseases and cancers, however their applicability to MAP infection in ruminants remains relatively unexplored. Here, we use a combination of small RNA sequencing and microarray data to explore circulating miRNA and mRNA responses of sheep infected with and resilient to MAP. A total of 58 differentially expressed miRNA were identified in only MAP infected sheep and 25 in only resilient sheep. Early and late timepoint specific signatures were also observed between infected and resilient sheep. Together, our data presents a novel miRNA signature of MAP infection, and resilience to infection. Further, we identify key signalling and immune pathways regulated by these miRNA which may contribute to the resilience phenotype and the ability of these sheep to prevent infection.